Using two different cell-mediated responses (secondary lymphocyte proliferative responses and secondary cell-mediate cytotoxicity) we have continued to probe the complexities of the alloantigenic differences between normal human donors. Rapid progress has continued in defining the genetics, structure and function of the HLA-SB antigens (defined in our lab) through local and collaborative studies. Monoclonal antibodies against human and mouse class II antigens have systematically been screened for their pattern of binding to products of different subregions of HLA distinguished by deletion mutant, and for their ability to inhibit proliferative and cytotoxic responses to the 5 SB alleles; these studies begin to reveal simplifying patterns amidst the complicated patterns of cross-reactivity among class II locus products. Some promising alloantisera are continuing to be evaluated for SB reactivity. T cell cloning studies reveal remarkable lack of heterogeneity of T cells recognizing the SB alleles, except for SB4. Structural studies are in progress at the level of identification of the SB genes. Efforts have been initiated to systematically examine cellular reactivity to human minor histocompatibility antigens. Such responses were first observed from leukocytes of a normal women potentially primed during pregnancy. New approaches allow the generation of minor antigen specific clones from lymphocytes of unprimed donors and promise to be powerful tools for the systematic analysis of these antigens.